The Effect of GLP-1 Receptor Agonists on Hidradenitis Suppurativa: A Comprehensive Systematic Review

Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory skin disorder affecting apocrine gland–bearing areas such as the axillae, inguinal regions, and anogenital area.¹ It manifests with painful nodules, abscesses, sinus tract formation, and scarring.² The disease strongly impacts patients’ quality of life due to pain, malodor, and psychosocial burden.³

The exact etiology of HS is multifactorial, involving genetic predisposition, mechanical stress, hormonal influences, dysbiosis, and immune dysregulation.⁴ Obesity and metabolic syndrome are highly prevalent among patients with HS and are considered exacerbating factors.⁵ Adipose tissue contributes to systemic inflammation through the secretion of proinflammatory cytokines such as tumor necrosis factor (TNF) α and interleukins (ILs).⁶

Management of HS includes lifestyle modifications, medical therapy, and surgical interventions. Medical treatments encompass antibiotics, retinoids, hormonal therapy, immunosuppressants, and immunomodulators such as anti-TNF and anti–IL-17 agents.⁷ Despite available therapies, many patients have suboptimal responses or experience adverse effects and dramatic reductions in their quality of life.³

Glucagonlike peptide 1 receptor agonists (GLP-1 RAs) are incretin-based therapies used in type 2 diabetes and obesity management.⁸ They enhance insulin secretion, suppress glucagon release, delay gastric emptying, and promote satiety.⁹ Beyond glycemic control, GLP-1 RAs exhibit anti-inflammatory properties and cardiovascular benefits.¹⁰

Given the high prevalence of obesity and metabolic syndrome in patients with HS as well as the anti-inflammatory effects of GLP-1 RAs, these agents may offer therapeutic benefits in HS.¹¹ We conducted a systematic review to evaluate the existing evidence on the efficacy and safety of GLP-1 RAs in the treatment of HS.

Methods

A systematic review was conducted via a PubMed search of articles indexed for MEDLINE in October 2024, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines¹² using the terms hidradenitis suppurativa OR acne inversa AND GLP-1 receptor agonist OR glucagon-like peptide-1 receptor agonist OR liraglutide OR semaglutide OR exenatide OR dulaglutide. No filters were applied to limit the search by language or publication date.

Inclusion criteria were clinical trials, observational studies (cohort, case control, cross-sectional), and case reports/series involving patients diagnosed with HS treated with GLP-1 RAs. Outcomes of interest included clinical improvement in HS severity (eg, lesion count, pain assessment, HS-specific scores), safety, and adverse events. Exclusion criteria included animal studies or in vitro experiments, reviews, editorials, and opinion pieces without original patient data; studies not in English; and studies not reporting clinical outcomes related to HS.

Two independent reviewers (N.R.K. and S.K.C.) screened the titles and abstracts for relevance. Full-text articles of potentially eligible studies were retrieved for detailed evaluation. Data extracted included study design, patient demographics, intervention details, outcomes, and adverse events. Discrepancies were resolved through discussion.

Results

The initial search yielded 11 articles (Figure). After screening titles and abstracts, 9 articles were selected for full-text review. Of these, 3 articles met the inclusion criteria. These studies included 3 case reports. Interventions involved liraglutide (2 reports)^13,14 and semaglutide¹⁵ (1 report)(Table). The patient population consisted of adult patients with HS with comorbid diabetes, obesity, and/or metabolic syndrome.

Jennings et al¹³ reported a 31-year-old obese woman with a history of smoking and Hurley stage 2 HS, a Hidradenitis Suppurativa Physician’s Global Assessment score of 4, a Dermatology Life Quality Index score of 24, and a body mass index of 45.3. She was treated with liraglutide monotherapy, starting with 0.6 mg subcutaneously once daily then titrating weekly to 1.8 mg subcutaneously. After 4 weeks, outcomes showed a reduction in Hidradenitis Suppurativa Physician’s Global Assessment (score=1) and Dermatology Life Quality Index (score=14) scores, and the patient lost 4.5 kg from baseline. The patient’s Hurley stage decreased from 2 to 1. After another 4 weeks, the patient’s weight decreased by a further 2 kg and HS remained controlled. No adverse events were recorded.

Khandalavala¹⁴ reported a single case of a 19-year-old woman with severe HS, obesity, and metabolic syndrome of 8 years’ duration treated with liraglutide. The patient had a weight of 215 lb with a body mass index of 37. With a combination of metformin 2000 mg/d, liraglutide 0.6 mg/d subcutaneously increased to 1.8 mg/d over 2 months, levonorgestrel-ethinyl estradiol (no dosage listed), dapsone 100 mg/d, and finasteride 5 mg/d, there was a marked reduction in nodules and abscesses after 6 months, with a weight loss of 40 lb (19% body weight). No adverse events were reported.

Mainville et al¹⁵ described a 59-year-old woman with refractory HS who showed improvement with a combination of intravenous ertapenem 1 g/d for 6 weeks, minocycline 100 mg/d for 3 months, metformin 500 mg three times daily for 2 months, doxycycline 100 mg/d to bridge to adalimumab (160 mg subcutaneously starting dose then 80 mg subcutaneously), and semaglutide (no dosage listed). After semaglutide was introduced, the patient lost 10 kg. The only adverse event was diarrhea.

Comment

The limited but growing body of evidence suggests that GLP-1 RAs may be beneficial in managing HS, particularly in patients with comorbid obesity. Treatment with liraglutide or semaglutide was associated with marked improvements in clinical severity scores, lesion counts, pain reduction, and quality of life.

As adjunct therapy, GLP-1 RAs could serve alongside standard HS treatments such as antibiotics and biologics. Addressing obesity, a known risk factor and disease modifier in HS, may lead to better disease control. The therapeutic benefits of GLP-1 RAs in HS are attributed to weight loss, which reduces adipose tissue and systemic inflammation.¹⁶ The anti-inflammatory effects of GLP-1 RAs involve the reduction of proinflammatory cytokines such as IL-6 and TNF-α.¹⁷ Metabolic improvements, including enhanced insulin sensitivity and lipid profile, also may contribute to disease modulation.¹⁷

Limitations—Because our analysis was limited to 3 case reports, the strength of the evidence is limited. These case reports also lack the standardized use of the Hidradenitis Suppurativa Clinical Response scoring system that generally is found in randomized controlled trials (RCTs). The lack of RCTs precludes definitive conclusions about efficacy. Future directions include the need for well-designed RCTs with large sample sizes to confirm findings, assessment of long-term safety and tolerability in patients with HS, and further research into the molecular mechanisms by which GLP-1 RAs affect HS pathophysiology. Of note, it is imperative to be aware of the medication shortage for all GLP-1 RAs when prescribing these medications for patients with HS.

Conclusion

Glucagonlike peptide 1 RAs show promise as a therapeutic option for HS, especially in patients with obesity and metabolic disturbances. The observed benefits likely result from weight loss and anti-inflammatory effects. Other drugs targeting glucose-dependent insulinotropic polypeptide and glucagon also are being studied thoroughly as options for managing HS. Although preliminary results are encouraging, robust clinical trials are needed to establish efficacy, optimal dosing, and safety in this patient population.